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Tackling the massive threat of climate change
Soon after moving to Pittsburgh for my pulmonary and critical care medicine fellowship in 2014, I began noticing a theme: So many of my patients expressed a sense that the air they breathed was harming them or was in some way responsible for the severity of their lung disease.
In this city, the legacy of the steel industry from the last century fostered economic prosperity but resulted in a profound legacy of pollution as well. Unfortunately, due to a combination of fossil fuel dependence for electricity generation and transportation, industrial particulate matter (PM) generation and greenhouse gas emissions, temperature inversions related to the topography of the region, and, most recently, smoke from Canadian wildfires in the summer of 2023, the air quality in Pittsburgh ranks among the 25 least healthy US cities. Our patients are bearing the burden of climate change.
I remember a patient in clinic talking about how on the days he could see a film of particulate on all the cars and the street outside, he knew he would feel more shortness of breath. Patients share about how when they had lived in different neighborhoods in town or traveled outside of Pittsburgh, their breathing improved.
Patients tell me that their asthma or COPD that did not use to cause them frequent trouble is now less well controlled despite better therapies available. Patients who used to experience seasonal allergies in just the fall or the spring now are plagued by their allergy symptoms year-round because of a warming climate yielding excess pollen throughout all seasons.
A recent study of patients with pulmonary fibrosis demonstrated that exposure to excess PM2.5 in this region resulted in more rapid clinical deterioration and premature death compared with patients with the same disease in other parts of North America with better air quality. The common denominator is human-generated climate change’s negative impact on health.
In particular, those who are already vulnerable because of underlying chronic disease or socioeconomic disparity are at greater risk and feel these repercussions disproportionately. Black and brown communities are more heavily exposed to air pollution due to the history of redlining and ongoing structural racism and, as a result, have worse health outcomes than other groups. There is an urgency and moral imperative for us as clinicians to address generations of environmental injustice.
While these themes floated around in the background during the early stage of my career as a pulmonologist, I didn’t have language or deep knowledge around these structural environmental issues. As a profession, we are gradually recognizing that the health impacts of climate change on which to advocate are within our wheelhouse as clinicians.
Our patients and our trainees are increasingly aware of these issues, and, as a result, we as currently practicing clinicians and educators must urgently learn about the lived experiences of our patients and how their diseases interplay with their exposures.
Nowadays, I think more about how to mitigate the impact of air pollution, which did not previously factor into my training or the early years of my clinical practice. We know that some patients, particularly those with underlying lung disease and young children, are at greater risk when exposed to more polluted air and may need to take different steps to limit their exposure. We now consider advising these patients with chronic respiratory disease to be aware of air quality advisories and limit their time outdoors on worse air quality days. We anticipate that when the air quality is worse, we will see more complications of cardiovascular and pulmonary disease.
As lifelong learners, we thirst for the latest data to incorporate into our clinical decision-making. Similarly, colleagues and I are now also voraciously reading and starting to have conversations with peers about the convergence of climate change and disease. But no matter how compelling and urgent these issues are, one clinician cannot tackle the massive threat of climate change and complexity of health care sustainability in isolation.
I am fortunate to work with several like-minded and highly motivated colleagues at my own institution. We have been able to organize effectively to spark local change toward reducing our system’s carbon emissions. Similarly, through professional organizations like CHEST, I have been able to collaborate with other pulmonary and critical care clinicians who share these passions and are doing similar advocacy work across the country. I am honored to serve as CHEST’s representative to the Medical Society Consortium on Climate and Health as another avenue to keep advancing this cause at scale in collaboration with advocates across all specialties.
While I worry every day for my patients, our communities, and my children as we face the accelerating threat of climate change, knowing that I am actively engaging in these efforts in pursuit of environmental justice and mitigating health care’s climate change contribution gives me a sense of empowerment and solidarity with others also striving to lessen our burden on the planet.
This article was adapted from the Winter 2024 online issue of CHEST Advocates. For the full article — and to engage with the other content from this issue — visit https://chestnet.org/chest-advocates.
Soon after moving to Pittsburgh for my pulmonary and critical care medicine fellowship in 2014, I began noticing a theme: So many of my patients expressed a sense that the air they breathed was harming them or was in some way responsible for the severity of their lung disease.
In this city, the legacy of the steel industry from the last century fostered economic prosperity but resulted in a profound legacy of pollution as well. Unfortunately, due to a combination of fossil fuel dependence for electricity generation and transportation, industrial particulate matter (PM) generation and greenhouse gas emissions, temperature inversions related to the topography of the region, and, most recently, smoke from Canadian wildfires in the summer of 2023, the air quality in Pittsburgh ranks among the 25 least healthy US cities. Our patients are bearing the burden of climate change.
I remember a patient in clinic talking about how on the days he could see a film of particulate on all the cars and the street outside, he knew he would feel more shortness of breath. Patients share about how when they had lived in different neighborhoods in town or traveled outside of Pittsburgh, their breathing improved.
Patients tell me that their asthma or COPD that did not use to cause them frequent trouble is now less well controlled despite better therapies available. Patients who used to experience seasonal allergies in just the fall or the spring now are plagued by their allergy symptoms year-round because of a warming climate yielding excess pollen throughout all seasons.
A recent study of patients with pulmonary fibrosis demonstrated that exposure to excess PM2.5 in this region resulted in more rapid clinical deterioration and premature death compared with patients with the same disease in other parts of North America with better air quality. The common denominator is human-generated climate change’s negative impact on health.
In particular, those who are already vulnerable because of underlying chronic disease or socioeconomic disparity are at greater risk and feel these repercussions disproportionately. Black and brown communities are more heavily exposed to air pollution due to the history of redlining and ongoing structural racism and, as a result, have worse health outcomes than other groups. There is an urgency and moral imperative for us as clinicians to address generations of environmental injustice.
While these themes floated around in the background during the early stage of my career as a pulmonologist, I didn’t have language or deep knowledge around these structural environmental issues. As a profession, we are gradually recognizing that the health impacts of climate change on which to advocate are within our wheelhouse as clinicians.
Our patients and our trainees are increasingly aware of these issues, and, as a result, we as currently practicing clinicians and educators must urgently learn about the lived experiences of our patients and how their diseases interplay with their exposures.
Nowadays, I think more about how to mitigate the impact of air pollution, which did not previously factor into my training or the early years of my clinical practice. We know that some patients, particularly those with underlying lung disease and young children, are at greater risk when exposed to more polluted air and may need to take different steps to limit their exposure. We now consider advising these patients with chronic respiratory disease to be aware of air quality advisories and limit their time outdoors on worse air quality days. We anticipate that when the air quality is worse, we will see more complications of cardiovascular and pulmonary disease.
As lifelong learners, we thirst for the latest data to incorporate into our clinical decision-making. Similarly, colleagues and I are now also voraciously reading and starting to have conversations with peers about the convergence of climate change and disease. But no matter how compelling and urgent these issues are, one clinician cannot tackle the massive threat of climate change and complexity of health care sustainability in isolation.
I am fortunate to work with several like-minded and highly motivated colleagues at my own institution. We have been able to organize effectively to spark local change toward reducing our system’s carbon emissions. Similarly, through professional organizations like CHEST, I have been able to collaborate with other pulmonary and critical care clinicians who share these passions and are doing similar advocacy work across the country. I am honored to serve as CHEST’s representative to the Medical Society Consortium on Climate and Health as another avenue to keep advancing this cause at scale in collaboration with advocates across all specialties.
While I worry every day for my patients, our communities, and my children as we face the accelerating threat of climate change, knowing that I am actively engaging in these efforts in pursuit of environmental justice and mitigating health care’s climate change contribution gives me a sense of empowerment and solidarity with others also striving to lessen our burden on the planet.
This article was adapted from the Winter 2024 online issue of CHEST Advocates. For the full article — and to engage with the other content from this issue — visit https://chestnet.org/chest-advocates.
Soon after moving to Pittsburgh for my pulmonary and critical care medicine fellowship in 2014, I began noticing a theme: So many of my patients expressed a sense that the air they breathed was harming them or was in some way responsible for the severity of their lung disease.
In this city, the legacy of the steel industry from the last century fostered economic prosperity but resulted in a profound legacy of pollution as well. Unfortunately, due to a combination of fossil fuel dependence for electricity generation and transportation, industrial particulate matter (PM) generation and greenhouse gas emissions, temperature inversions related to the topography of the region, and, most recently, smoke from Canadian wildfires in the summer of 2023, the air quality in Pittsburgh ranks among the 25 least healthy US cities. Our patients are bearing the burden of climate change.
I remember a patient in clinic talking about how on the days he could see a film of particulate on all the cars and the street outside, he knew he would feel more shortness of breath. Patients share about how when they had lived in different neighborhoods in town or traveled outside of Pittsburgh, their breathing improved.
Patients tell me that their asthma or COPD that did not use to cause them frequent trouble is now less well controlled despite better therapies available. Patients who used to experience seasonal allergies in just the fall or the spring now are plagued by their allergy symptoms year-round because of a warming climate yielding excess pollen throughout all seasons.
A recent study of patients with pulmonary fibrosis demonstrated that exposure to excess PM2.5 in this region resulted in more rapid clinical deterioration and premature death compared with patients with the same disease in other parts of North America with better air quality. The common denominator is human-generated climate change’s negative impact on health.
In particular, those who are already vulnerable because of underlying chronic disease or socioeconomic disparity are at greater risk and feel these repercussions disproportionately. Black and brown communities are more heavily exposed to air pollution due to the history of redlining and ongoing structural racism and, as a result, have worse health outcomes than other groups. There is an urgency and moral imperative for us as clinicians to address generations of environmental injustice.
While these themes floated around in the background during the early stage of my career as a pulmonologist, I didn’t have language or deep knowledge around these structural environmental issues. As a profession, we are gradually recognizing that the health impacts of climate change on which to advocate are within our wheelhouse as clinicians.
Our patients and our trainees are increasingly aware of these issues, and, as a result, we as currently practicing clinicians and educators must urgently learn about the lived experiences of our patients and how their diseases interplay with their exposures.
Nowadays, I think more about how to mitigate the impact of air pollution, which did not previously factor into my training or the early years of my clinical practice. We know that some patients, particularly those with underlying lung disease and young children, are at greater risk when exposed to more polluted air and may need to take different steps to limit their exposure. We now consider advising these patients with chronic respiratory disease to be aware of air quality advisories and limit their time outdoors on worse air quality days. We anticipate that when the air quality is worse, we will see more complications of cardiovascular and pulmonary disease.
As lifelong learners, we thirst for the latest data to incorporate into our clinical decision-making. Similarly, colleagues and I are now also voraciously reading and starting to have conversations with peers about the convergence of climate change and disease. But no matter how compelling and urgent these issues are, one clinician cannot tackle the massive threat of climate change and complexity of health care sustainability in isolation.
I am fortunate to work with several like-minded and highly motivated colleagues at my own institution. We have been able to organize effectively to spark local change toward reducing our system’s carbon emissions. Similarly, through professional organizations like CHEST, I have been able to collaborate with other pulmonary and critical care clinicians who share these passions and are doing similar advocacy work across the country. I am honored to serve as CHEST’s representative to the Medical Society Consortium on Climate and Health as another avenue to keep advancing this cause at scale in collaboration with advocates across all specialties.
While I worry every day for my patients, our communities, and my children as we face the accelerating threat of climate change, knowing that I am actively engaging in these efforts in pursuit of environmental justice and mitigating health care’s climate change contribution gives me a sense of empowerment and solidarity with others also striving to lessen our burden on the planet.
This article was adapted from the Winter 2024 online issue of CHEST Advocates. For the full article — and to engage with the other content from this issue — visit https://chestnet.org/chest-advocates.
CHEST grant recipient studying increase in lung cancer diagnoses among Chinese American women
In his prior research, Chien-Ching Li, PhD, MPH, focused on promoting lung cancer screening in Chinese American men, a population that frequently smokes heavily. But last year, he applied for a CHEST grant that’s shifting his focus to another demographic: Chinese American women who do not smoke, especially those with limited English proficiency.
“They are developing lung cancer, and we don’t know why,” said Dr. Li, an associate professor of Health Systems Management at Rush University.
In fact, 57% of Asian American women diagnosed with lung cancer never smoked cigarettes.
What’s behind this rise in lung cancer in women who have never smoked compared with men, and particularly in Asian American women? One possibility: While Chinese American women may never smoke themselves, they frequently live with partners or family members who do. (About 28% of Chinese American men smoke heavily, Dr. Li said.)
“We think secondhand smoke might be one of the key risk factors, because they’re living with people who smoke,” Dr. Li said. His prior research shows that the majority of Chinese American men in greater Chicagoland—89%—are married, and many of them smoke or have a history of smoking.
With the CHEST grant Dr. Li received in October 2023, he’s working to increase awareness among Chinese American women about the risks of secondhand smoke and “reduce the health disparity in lung cancer among women,” Dr. Li said.
Developing culturally sensitive materials for a high-risk group
While many lung cancer reduction efforts focus on people who smoke, there are plenty of pamphlets designed to inform about the risks incurred when breathing in secondhand smoke.
These handouts, however, aren’t always available in languages spoken by Chinese Americans. Nor is it as simple as hiring a translator; doing so may make the pamphlets readable to the women, but it won’t necessarily make the text culturally appropriate.
This is what Dr. Li—along with his coinvestigators, Alicia Matthews, PhD, a professor of clinical psychology at Columbia University, and Hong Liu, PhD, of the Midwest Asian Health Association—seeks to change, with funding from the CHEST grant. Their goal is four-pronged:
1. Discovery: Dr. Li and his team are currently surveying Chinese American women who have never smoked but who live with people who smoke in greater Chicagoland. These surveys will help them learn more about what (if anything) this group knows about the health risks associated with secondhand smoke and other types of environmental smoke.
2. Identify: These surveys, along with focus group interviews with select participants, will help reveal barriers standing in the way of reducing the women’s exposure to secondhand smoke—as well as ways to encourage habits to reduce risk.
3. Develop: All the information gained through surveys and conversations will then be analyzed and used to craft targeted, translated, and culturally appropriate materials on secondhand smoke, conveying communication strategies the women can use to persuade their partners to quit smoking and ways to build a smoke-free household.
4. Evaluate: The effectiveness of the new materials will be tested to assess the change in the women’s knowledge, as well as any uptick in taking steps to reduce exposure or sign up for screening.
Using the CHEST grant as a building block to more grants—and more information
Dr. Li and his collaborators are still in the early stages of using the CHEST grant: gathering up participants and surveying them.
But there’s much ahead. With the CHEST grant in hand, Dr. Li plans to apply for grants from the National Institutes of Health (NIH): first, an NIH Exploratory/Developmental Research Grant Award (R21) to help achieve that fourth aim of evaluating how the intervention works. And next, they’ll apply for an NIH Research Project Grant Program (R01), which will fund an even larger trial.
“Not many studies focus on identifying the risk factors with lung cancer associated with Chinese American [women who have never smoked],” Dr. Li said. “This is why we want to focus on this area to provide more knowledge and make more contributions to research.”
Projects like this are made possible by generous contributions from CHEST donors. Support the future of chest medicine by visiting https://chestnet.org/donate.
In his prior research, Chien-Ching Li, PhD, MPH, focused on promoting lung cancer screening in Chinese American men, a population that frequently smokes heavily. But last year, he applied for a CHEST grant that’s shifting his focus to another demographic: Chinese American women who do not smoke, especially those with limited English proficiency.
“They are developing lung cancer, and we don’t know why,” said Dr. Li, an associate professor of Health Systems Management at Rush University.
In fact, 57% of Asian American women diagnosed with lung cancer never smoked cigarettes.
What’s behind this rise in lung cancer in women who have never smoked compared with men, and particularly in Asian American women? One possibility: While Chinese American women may never smoke themselves, they frequently live with partners or family members who do. (About 28% of Chinese American men smoke heavily, Dr. Li said.)
“We think secondhand smoke might be one of the key risk factors, because they’re living with people who smoke,” Dr. Li said. His prior research shows that the majority of Chinese American men in greater Chicagoland—89%—are married, and many of them smoke or have a history of smoking.
With the CHEST grant Dr. Li received in October 2023, he’s working to increase awareness among Chinese American women about the risks of secondhand smoke and “reduce the health disparity in lung cancer among women,” Dr. Li said.
Developing culturally sensitive materials for a high-risk group
While many lung cancer reduction efforts focus on people who smoke, there are plenty of pamphlets designed to inform about the risks incurred when breathing in secondhand smoke.
These handouts, however, aren’t always available in languages spoken by Chinese Americans. Nor is it as simple as hiring a translator; doing so may make the pamphlets readable to the women, but it won’t necessarily make the text culturally appropriate.
This is what Dr. Li—along with his coinvestigators, Alicia Matthews, PhD, a professor of clinical psychology at Columbia University, and Hong Liu, PhD, of the Midwest Asian Health Association—seeks to change, with funding from the CHEST grant. Their goal is four-pronged:
1. Discovery: Dr. Li and his team are currently surveying Chinese American women who have never smoked but who live with people who smoke in greater Chicagoland. These surveys will help them learn more about what (if anything) this group knows about the health risks associated with secondhand smoke and other types of environmental smoke.
2. Identify: These surveys, along with focus group interviews with select participants, will help reveal barriers standing in the way of reducing the women’s exposure to secondhand smoke—as well as ways to encourage habits to reduce risk.
3. Develop: All the information gained through surveys and conversations will then be analyzed and used to craft targeted, translated, and culturally appropriate materials on secondhand smoke, conveying communication strategies the women can use to persuade their partners to quit smoking and ways to build a smoke-free household.
4. Evaluate: The effectiveness of the new materials will be tested to assess the change in the women’s knowledge, as well as any uptick in taking steps to reduce exposure or sign up for screening.
Using the CHEST grant as a building block to more grants—and more information
Dr. Li and his collaborators are still in the early stages of using the CHEST grant: gathering up participants and surveying them.
But there’s much ahead. With the CHEST grant in hand, Dr. Li plans to apply for grants from the National Institutes of Health (NIH): first, an NIH Exploratory/Developmental Research Grant Award (R21) to help achieve that fourth aim of evaluating how the intervention works. And next, they’ll apply for an NIH Research Project Grant Program (R01), which will fund an even larger trial.
“Not many studies focus on identifying the risk factors with lung cancer associated with Chinese American [women who have never smoked],” Dr. Li said. “This is why we want to focus on this area to provide more knowledge and make more contributions to research.”
Projects like this are made possible by generous contributions from CHEST donors. Support the future of chest medicine by visiting https://chestnet.org/donate.
In his prior research, Chien-Ching Li, PhD, MPH, focused on promoting lung cancer screening in Chinese American men, a population that frequently smokes heavily. But last year, he applied for a CHEST grant that’s shifting his focus to another demographic: Chinese American women who do not smoke, especially those with limited English proficiency.
“They are developing lung cancer, and we don’t know why,” said Dr. Li, an associate professor of Health Systems Management at Rush University.
In fact, 57% of Asian American women diagnosed with lung cancer never smoked cigarettes.
What’s behind this rise in lung cancer in women who have never smoked compared with men, and particularly in Asian American women? One possibility: While Chinese American women may never smoke themselves, they frequently live with partners or family members who do. (About 28% of Chinese American men smoke heavily, Dr. Li said.)
“We think secondhand smoke might be one of the key risk factors, because they’re living with people who smoke,” Dr. Li said. His prior research shows that the majority of Chinese American men in greater Chicagoland—89%—are married, and many of them smoke or have a history of smoking.
With the CHEST grant Dr. Li received in October 2023, he’s working to increase awareness among Chinese American women about the risks of secondhand smoke and “reduce the health disparity in lung cancer among women,” Dr. Li said.
Developing culturally sensitive materials for a high-risk group
While many lung cancer reduction efforts focus on people who smoke, there are plenty of pamphlets designed to inform about the risks incurred when breathing in secondhand smoke.
These handouts, however, aren’t always available in languages spoken by Chinese Americans. Nor is it as simple as hiring a translator; doing so may make the pamphlets readable to the women, but it won’t necessarily make the text culturally appropriate.
This is what Dr. Li—along with his coinvestigators, Alicia Matthews, PhD, a professor of clinical psychology at Columbia University, and Hong Liu, PhD, of the Midwest Asian Health Association—seeks to change, with funding from the CHEST grant. Their goal is four-pronged:
1. Discovery: Dr. Li and his team are currently surveying Chinese American women who have never smoked but who live with people who smoke in greater Chicagoland. These surveys will help them learn more about what (if anything) this group knows about the health risks associated with secondhand smoke and other types of environmental smoke.
2. Identify: These surveys, along with focus group interviews with select participants, will help reveal barriers standing in the way of reducing the women’s exposure to secondhand smoke—as well as ways to encourage habits to reduce risk.
3. Develop: All the information gained through surveys and conversations will then be analyzed and used to craft targeted, translated, and culturally appropriate materials on secondhand smoke, conveying communication strategies the women can use to persuade their partners to quit smoking and ways to build a smoke-free household.
4. Evaluate: The effectiveness of the new materials will be tested to assess the change in the women’s knowledge, as well as any uptick in taking steps to reduce exposure or sign up for screening.
Using the CHEST grant as a building block to more grants—and more information
Dr. Li and his collaborators are still in the early stages of using the CHEST grant: gathering up participants and surveying them.
But there’s much ahead. With the CHEST grant in hand, Dr. Li plans to apply for grants from the National Institutes of Health (NIH): first, an NIH Exploratory/Developmental Research Grant Award (R21) to help achieve that fourth aim of evaluating how the intervention works. And next, they’ll apply for an NIH Research Project Grant Program (R01), which will fund an even larger trial.
“Not many studies focus on identifying the risk factors with lung cancer associated with Chinese American [women who have never smoked],” Dr. Li said. “This is why we want to focus on this area to provide more knowledge and make more contributions to research.”
Projects like this are made possible by generous contributions from CHEST donors. Support the future of chest medicine by visiting https://chestnet.org/donate.
Hospitals Cash In on a Private Equity-Backed Trend: Concierge Physician Care
Nonprofit hospitals created largely to serve the poor are adding concierge physician practices, charging patients annual membership fees of $2,000 or more for easier access to their doctors.
It’s a trend that began decades ago with physician practices. Thousands of doctors have shifted to the concierge model, in which they can increase their income while decreasing their patient load.
Northwestern Medicine in Chicago, Penn Medicine in Philadelphia, University Hospitals in the Cleveland area, and Baptist Health in Miami are among the large hospital systems offering concierge physician services. The fees, which can exceed $4,000 a year, are in addition to copayments, deductibles, and other charges not paid by patients’ insurance plans.
Critics of concierge medicine say the practice exacerbates primary care shortages, ensuring access only for the affluent, while driving up health care costs. But for tax-exempt hospitals, the financial benefits can be twofold.
“Hospitals are attracted to physicians that offer concierge services because their patients do not come with bad debts or a need for charity care, and most of them have private insurance which pays the hospital very well,” said Gerard Anderson, a hospital finance expert at Johns Hopkins University.
“They are the ideal patient, from the hospitals’ perspective.”
Concierge physicians typically limit their practices to a few hundred patients, compared with a couple of thousand for a traditional primary care doctor, so they can promise immediate access and longer visits.
“Every time we see these models expand, we are contracting the availability of primary care doctors for the general population,” said Jewel Mullen, associate dean for health equity at the University of Texas-Austin’s Dell Medical School. The former Connecticut health commissioner said concierge doctors join large hospital systems because of the institutions’ reputations, while hospitals sign up concierge physicians to ensure referrals to specialists and inpatient care. “It helps hospitals secure a bigger piece of their market,” she said.
Concierge physicians typically promise same-day or next-day appointments. Many provide patients their mobile phone number.
Aaron Klein, who oversees the concierge physician practices at Baptist Health, said the program was initially intended to serve donors.
“High-end donors wanted to make sure they have doctors to care for them,” he said.
Baptist opened its concierge program in 2019 and now has three practices across South Florida, where patients pay $2,500 a year.
“My philosophy is: It’s better to give world-class care to a few hundred patients rather than provide inadequate care to a few thousand patients,” Klein said.
Concierge physician practices started more than 20 years ago, mainly in upscale areas such as Boca Raton, Florida, and La Jolla, California. They catered mostly to wealthy retirees willing to pay extra for better physician access. Some of the first physician practices to enter the business were backed by private equity firms.
One of the largest, Boca Raton-based MDVIP, has more than 1,100 physicians and more than 390,000 patients. It was started in 2000, and since 2014 private equity firms have owned a majority stake in the company.
Some concierge physicians say their more attentive care means healthier patients. A study published last year by researchers at the University of California-Berkeley and University of Pennsylvania found no impact on mortality rates. What the study did find: higher costs.
Using Medicare claims data, the researchers found that concierge medicine enrollment corresponded with a 30%-50% increase in total health care spending by patients.
For hospitals, “this is an extension of them consolidating the market,” said Adam Leive, a study co-author and an assistant professor of public policy at UC Berkeley. Inova Health Care Services in Fairfax, Virginia, one of the state’s largest tax-exempt hospital chains, employs 18 concierge doctors, who each handle no more than 400 patients. Those patients pay $2,200 a year for the privilege.
George Salem, 70, of McLean, Virginia, has been a patient in Inova’s concierge practice for several years along with his wife. Earlier this year he slammed his finger in a hotel door, he said. As soon as he got home, he called his physician, who saw him immediately and stitched up the wound. He said he sees his doctor about 10 to 12 times a year.
“I loved my internist before, but it was impossible to get to see him,” Salem said. Immediate access to his doctor “very much gives me peace of mind,” he said.
Craig Cheifetz, a vice president at Inova who oversees the concierge program, said the hospital system took interest in the model after MDVIP began moving aggressively into the Washington, D.C., suburbs about a decade ago. Today, Inova’s program has 6,000 patients.
Cheifetz disputes the charge that concierge physician programs exacerbate primary care shortages. The model keeps doctors who were considering retiring early in the business with a lighter caseload, he said. And the fees amount to no more than a few dollars a day — about what some people spend on coffee, he said.
“Inova has an incredible primary care network for those who can’t afford the concierge care,” he said. “We are still providing all that is necessary in primary care for those who need it.”
Some hospitals are starting concierge physician practices far from their home locations. For example, Tampa General Hospital in Florida last year opened a concierge practice in upper-middle-class Palm Beach Gardens, a roughly three-hour drive from Tampa. Mount Sinai Health System in New York runs a concierge physician practice in West Palm Beach.
NCH Healthcare System in Naples, Florida, employs 12 concierge physicians who treat about 3,000 patients total. “We found a need in this community for those who wanted a more personalized health care experience,” said James Brinkert, regional administrator for the system. Members pay an annual fee of at least $3,500.
NCH patients whose doctors convert to concierge and who don’t want to pay the membership fee are referred to other primary care practices or to urgent care, Brinkert said.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF .
Nonprofit hospitals created largely to serve the poor are adding concierge physician practices, charging patients annual membership fees of $2,000 or more for easier access to their doctors.
It’s a trend that began decades ago with physician practices. Thousands of doctors have shifted to the concierge model, in which they can increase their income while decreasing their patient load.
Northwestern Medicine in Chicago, Penn Medicine in Philadelphia, University Hospitals in the Cleveland area, and Baptist Health in Miami are among the large hospital systems offering concierge physician services. The fees, which can exceed $4,000 a year, are in addition to copayments, deductibles, and other charges not paid by patients’ insurance plans.
Critics of concierge medicine say the practice exacerbates primary care shortages, ensuring access only for the affluent, while driving up health care costs. But for tax-exempt hospitals, the financial benefits can be twofold.
“Hospitals are attracted to physicians that offer concierge services because their patients do not come with bad debts or a need for charity care, and most of them have private insurance which pays the hospital very well,” said Gerard Anderson, a hospital finance expert at Johns Hopkins University.
“They are the ideal patient, from the hospitals’ perspective.”
Concierge physicians typically limit their practices to a few hundred patients, compared with a couple of thousand for a traditional primary care doctor, so they can promise immediate access and longer visits.
“Every time we see these models expand, we are contracting the availability of primary care doctors for the general population,” said Jewel Mullen, associate dean for health equity at the University of Texas-Austin’s Dell Medical School. The former Connecticut health commissioner said concierge doctors join large hospital systems because of the institutions’ reputations, while hospitals sign up concierge physicians to ensure referrals to specialists and inpatient care. “It helps hospitals secure a bigger piece of their market,” she said.
Concierge physicians typically promise same-day or next-day appointments. Many provide patients their mobile phone number.
Aaron Klein, who oversees the concierge physician practices at Baptist Health, said the program was initially intended to serve donors.
“High-end donors wanted to make sure they have doctors to care for them,” he said.
Baptist opened its concierge program in 2019 and now has three practices across South Florida, where patients pay $2,500 a year.
“My philosophy is: It’s better to give world-class care to a few hundred patients rather than provide inadequate care to a few thousand patients,” Klein said.
Concierge physician practices started more than 20 years ago, mainly in upscale areas such as Boca Raton, Florida, and La Jolla, California. They catered mostly to wealthy retirees willing to pay extra for better physician access. Some of the first physician practices to enter the business were backed by private equity firms.
One of the largest, Boca Raton-based MDVIP, has more than 1,100 physicians and more than 390,000 patients. It was started in 2000, and since 2014 private equity firms have owned a majority stake in the company.
Some concierge physicians say their more attentive care means healthier patients. A study published last year by researchers at the University of California-Berkeley and University of Pennsylvania found no impact on mortality rates. What the study did find: higher costs.
Using Medicare claims data, the researchers found that concierge medicine enrollment corresponded with a 30%-50% increase in total health care spending by patients.
For hospitals, “this is an extension of them consolidating the market,” said Adam Leive, a study co-author and an assistant professor of public policy at UC Berkeley. Inova Health Care Services in Fairfax, Virginia, one of the state’s largest tax-exempt hospital chains, employs 18 concierge doctors, who each handle no more than 400 patients. Those patients pay $2,200 a year for the privilege.
George Salem, 70, of McLean, Virginia, has been a patient in Inova’s concierge practice for several years along with his wife. Earlier this year he slammed his finger in a hotel door, he said. As soon as he got home, he called his physician, who saw him immediately and stitched up the wound. He said he sees his doctor about 10 to 12 times a year.
“I loved my internist before, but it was impossible to get to see him,” Salem said. Immediate access to his doctor “very much gives me peace of mind,” he said.
Craig Cheifetz, a vice president at Inova who oversees the concierge program, said the hospital system took interest in the model after MDVIP began moving aggressively into the Washington, D.C., suburbs about a decade ago. Today, Inova’s program has 6,000 patients.
Cheifetz disputes the charge that concierge physician programs exacerbate primary care shortages. The model keeps doctors who were considering retiring early in the business with a lighter caseload, he said. And the fees amount to no more than a few dollars a day — about what some people spend on coffee, he said.
“Inova has an incredible primary care network for those who can’t afford the concierge care,” he said. “We are still providing all that is necessary in primary care for those who need it.”
Some hospitals are starting concierge physician practices far from their home locations. For example, Tampa General Hospital in Florida last year opened a concierge practice in upper-middle-class Palm Beach Gardens, a roughly three-hour drive from Tampa. Mount Sinai Health System in New York runs a concierge physician practice in West Palm Beach.
NCH Healthcare System in Naples, Florida, employs 12 concierge physicians who treat about 3,000 patients total. “We found a need in this community for those who wanted a more personalized health care experience,” said James Brinkert, regional administrator for the system. Members pay an annual fee of at least $3,500.
NCH patients whose doctors convert to concierge and who don’t want to pay the membership fee are referred to other primary care practices or to urgent care, Brinkert said.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF .
Nonprofit hospitals created largely to serve the poor are adding concierge physician practices, charging patients annual membership fees of $2,000 or more for easier access to their doctors.
It’s a trend that began decades ago with physician practices. Thousands of doctors have shifted to the concierge model, in which they can increase their income while decreasing their patient load.
Northwestern Medicine in Chicago, Penn Medicine in Philadelphia, University Hospitals in the Cleveland area, and Baptist Health in Miami are among the large hospital systems offering concierge physician services. The fees, which can exceed $4,000 a year, are in addition to copayments, deductibles, and other charges not paid by patients’ insurance plans.
Critics of concierge medicine say the practice exacerbates primary care shortages, ensuring access only for the affluent, while driving up health care costs. But for tax-exempt hospitals, the financial benefits can be twofold.
“Hospitals are attracted to physicians that offer concierge services because their patients do not come with bad debts or a need for charity care, and most of them have private insurance which pays the hospital very well,” said Gerard Anderson, a hospital finance expert at Johns Hopkins University.
“They are the ideal patient, from the hospitals’ perspective.”
Concierge physicians typically limit their practices to a few hundred patients, compared with a couple of thousand for a traditional primary care doctor, so they can promise immediate access and longer visits.
“Every time we see these models expand, we are contracting the availability of primary care doctors for the general population,” said Jewel Mullen, associate dean for health equity at the University of Texas-Austin’s Dell Medical School. The former Connecticut health commissioner said concierge doctors join large hospital systems because of the institutions’ reputations, while hospitals sign up concierge physicians to ensure referrals to specialists and inpatient care. “It helps hospitals secure a bigger piece of their market,” she said.
Concierge physicians typically promise same-day or next-day appointments. Many provide patients their mobile phone number.
Aaron Klein, who oversees the concierge physician practices at Baptist Health, said the program was initially intended to serve donors.
“High-end donors wanted to make sure they have doctors to care for them,” he said.
Baptist opened its concierge program in 2019 and now has three practices across South Florida, where patients pay $2,500 a year.
“My philosophy is: It’s better to give world-class care to a few hundred patients rather than provide inadequate care to a few thousand patients,” Klein said.
Concierge physician practices started more than 20 years ago, mainly in upscale areas such as Boca Raton, Florida, and La Jolla, California. They catered mostly to wealthy retirees willing to pay extra for better physician access. Some of the first physician practices to enter the business were backed by private equity firms.
One of the largest, Boca Raton-based MDVIP, has more than 1,100 physicians and more than 390,000 patients. It was started in 2000, and since 2014 private equity firms have owned a majority stake in the company.
Some concierge physicians say their more attentive care means healthier patients. A study published last year by researchers at the University of California-Berkeley and University of Pennsylvania found no impact on mortality rates. What the study did find: higher costs.
Using Medicare claims data, the researchers found that concierge medicine enrollment corresponded with a 30%-50% increase in total health care spending by patients.
For hospitals, “this is an extension of them consolidating the market,” said Adam Leive, a study co-author and an assistant professor of public policy at UC Berkeley. Inova Health Care Services in Fairfax, Virginia, one of the state’s largest tax-exempt hospital chains, employs 18 concierge doctors, who each handle no more than 400 patients. Those patients pay $2,200 a year for the privilege.
George Salem, 70, of McLean, Virginia, has been a patient in Inova’s concierge practice for several years along with his wife. Earlier this year he slammed his finger in a hotel door, he said. As soon as he got home, he called his physician, who saw him immediately and stitched up the wound. He said he sees his doctor about 10 to 12 times a year.
“I loved my internist before, but it was impossible to get to see him,” Salem said. Immediate access to his doctor “very much gives me peace of mind,” he said.
Craig Cheifetz, a vice president at Inova who oversees the concierge program, said the hospital system took interest in the model after MDVIP began moving aggressively into the Washington, D.C., suburbs about a decade ago. Today, Inova’s program has 6,000 patients.
Cheifetz disputes the charge that concierge physician programs exacerbate primary care shortages. The model keeps doctors who were considering retiring early in the business with a lighter caseload, he said. And the fees amount to no more than a few dollars a day — about what some people spend on coffee, he said.
“Inova has an incredible primary care network for those who can’t afford the concierge care,” he said. “We are still providing all that is necessary in primary care for those who need it.”
Some hospitals are starting concierge physician practices far from their home locations. For example, Tampa General Hospital in Florida last year opened a concierge practice in upper-middle-class Palm Beach Gardens, a roughly three-hour drive from Tampa. Mount Sinai Health System in New York runs a concierge physician practice in West Palm Beach.
NCH Healthcare System in Naples, Florida, employs 12 concierge physicians who treat about 3,000 patients total. “We found a need in this community for those who wanted a more personalized health care experience,” said James Brinkert, regional administrator for the system. Members pay an annual fee of at least $3,500.
NCH patients whose doctors convert to concierge and who don’t want to pay the membership fee are referred to other primary care practices or to urgent care, Brinkert said.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF .
MS and Epstein-Barr Virus: What Do We Know and Where Do We Go From Here?
The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.
Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.
While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
EBV Boosts MS Risk 32-Fold
EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).
Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”
According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.
“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.
The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”
However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
‘Additional Fuses Must Be Ignited’
It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.
“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.
He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”
Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.
Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
Antivirals May Place a Crucial Role in MS Control
While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.
Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.
Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.
Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.
The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.
Dr. Levy said this line of questioning is important.
However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
More Questions to Answer About EBV and MS
Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”
The molecular mimicry theory also opens up a potential treatment pathway.
A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
Could an EBV Vaccine Be the Answer?
On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?
Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?
Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.
There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.
“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.
Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
A version of this article appeared on Medscape.com.
The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.
Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.
While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
EBV Boosts MS Risk 32-Fold
EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).
Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”
According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.
“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.
The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”
However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
‘Additional Fuses Must Be Ignited’
It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.
“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.
He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”
Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.
Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
Antivirals May Place a Crucial Role in MS Control
While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.
Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.
Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.
Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.
The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.
Dr. Levy said this line of questioning is important.
However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
More Questions to Answer About EBV and MS
Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”
The molecular mimicry theory also opens up a potential treatment pathway.
A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
Could an EBV Vaccine Be the Answer?
On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?
Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?
Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.
There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.
“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.
Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
A version of this article appeared on Medscape.com.
The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.
Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.
While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
EBV Boosts MS Risk 32-Fold
EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).
Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”
According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.
“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.
The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”
However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
‘Additional Fuses Must Be Ignited’
It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.
“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.
He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”
Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.
Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
Antivirals May Place a Crucial Role in MS Control
While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.
Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.
Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.
Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.
The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.
Dr. Levy said this line of questioning is important.
However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
More Questions to Answer About EBV and MS
Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”
The molecular mimicry theory also opens up a potential treatment pathway.
A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
Could an EBV Vaccine Be the Answer?
On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?
Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?
Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.
There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.
“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.
Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
A version of this article appeared on Medscape.com.
Blood Cancer Emergencies: Hematologists’ Late-Night Calls
When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.
In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.
Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
Leukocytosis
Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.
“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”
Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.
“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”
Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.
There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
Tumor lysis syndrome
While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”
It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
Differentiation syndrome
According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.
A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”
In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.
“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”
In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.
Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.
When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.
In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.
Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
Leukocytosis
Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.
“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”
Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.
“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”
Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.
There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
Tumor lysis syndrome
While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”
It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
Differentiation syndrome
According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.
A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”
In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.
“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”
In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.
Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.
When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.
In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.
Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
Leukocytosis
Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.
“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”
Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.
“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”
Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.
There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
Tumor lysis syndrome
While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”
It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
Differentiation syndrome
According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.
A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”
In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.
“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”
In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.
Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.
Frozen Embryos: Legally Children? The End of IVF, Says Ethicist
This transcript has been edited for clarity.
I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.
They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.
This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).
IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.
When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.
It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?
Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.
The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.
In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.
I think you’re going to find that other states may be influenced to try to mimic the Alabama court decision, but if they do so, it’s going to mean ultimately the end — regardless of what Alabama legislature tried to do — of IVF.
That has a political consequence that I don’t think can be sustained by proponents of fetal personhood or embryo personhood. There is just too much momentum to support the use of IVF to try to create life to make that a politically viable situation.
Alabama may have its court ruling, but I think it’s going to have to pass legislation that overrules the view that embryos are children, not just trying to exempt IVF from the consequences of that view, if we’re going to see IVF possible in that state or anywhere else in the United States.
Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.
They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.
This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).
IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.
When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.
It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?
Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.
The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.
In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.
I think you’re going to find that other states may be influenced to try to mimic the Alabama court decision, but if they do so, it’s going to mean ultimately the end — regardless of what Alabama legislature tried to do — of IVF.
That has a political consequence that I don’t think can be sustained by proponents of fetal personhood or embryo personhood. There is just too much momentum to support the use of IVF to try to create life to make that a politically viable situation.
Alabama may have its court ruling, but I think it’s going to have to pass legislation that overrules the view that embryos are children, not just trying to exempt IVF from the consequences of that view, if we’re going to see IVF possible in that state or anywhere else in the United States.
Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.
They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.
This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).
IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.
When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.
It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?
Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.
The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.
In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.
I think you’re going to find that other states may be influenced to try to mimic the Alabama court decision, but if they do so, it’s going to mean ultimately the end — regardless of what Alabama legislature tried to do — of IVF.
That has a political consequence that I don’t think can be sustained by proponents of fetal personhood or embryo personhood. There is just too much momentum to support the use of IVF to try to create life to make that a politically viable situation.
Alabama may have its court ruling, but I think it’s going to have to pass legislation that overrules the view that embryos are children, not just trying to exempt IVF from the consequences of that view, if we’re going to see IVF possible in that state or anywhere else in the United States.
Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.
A version of this article appeared on Medscape.com.
A Prescription Checklist for Older Adults in ED
TOPLINE:
The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).
METHODOLOGY:
- The American Geriatrics Society (AGS) has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
- In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
- They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
- After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.
TAKEAWAY:
- The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
- Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
- The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
- However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.
IN PRACTICE:
“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.
SOURCE:
This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.
LIMITATIONS:
The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.
DISCLOSURES:
This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.
A version of this article appeared on Medscape.com.
TOPLINE:
The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).
METHODOLOGY:
- The American Geriatrics Society (AGS) has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
- In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
- They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
- After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.
TAKEAWAY:
- The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
- Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
- The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
- However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.
IN PRACTICE:
“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.
SOURCE:
This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.
LIMITATIONS:
The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.
DISCLOSURES:
This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.
A version of this article appeared on Medscape.com.
TOPLINE:
The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).
METHODOLOGY:
- The American Geriatrics Society (AGS) has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
- In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
- They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
- After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.
TAKEAWAY:
- The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
- Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
- The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
- However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.
IN PRACTICE:
“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.
SOURCE:
This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.
LIMITATIONS:
The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.
DISCLOSURES:
This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.
A version of this article appeared on Medscape.com.
Clinical Characteristics of Chronic Nonbacterial Osteomyelitis Can Predict Therapy Needs Over Time
CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.
Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.
CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.
“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
Findings Helpful for Counseling
Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”
There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.
A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.
To better understand how different clinical characteristics predict treatment needs, the researchers conducted a retrospective chart review of 234 patients who received a CNO diagnosis before age 18 and who established care in the Children’s Hospital Colorado’s CNO multidisciplinary clinic between January 2005 and July 2021. After excluding 70 patients, primarily due to inadequate follow-up for assessing treatment response, the researchers included 164 patients whose records they reviewed through January 2022.
The researchers assessed how multiple aspects of disease involvement, including unifocal or multifocal at diagnosis, ever having symmetric bone lesions, number of regions ever affected by CNO, complications, and disease activity at most recent follow-up, to determine their relationship to the total number of days on NSAID monotherapy and the odds of needing a second-line treatment.
Among the 164 patients in the study, 32 had a short course of NSAIDs (3-7 months), 62 had a long course of NSAIDs (7 or more months), and 70 received second-line treatment.
Findings From Largest Single-Center Cohort in North America
Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.
There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).
Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).
More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).
There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).
None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).
At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).
This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.
Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.
“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.
Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.
A version of this article appeared on Medscape.com .
CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.
Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.
CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.
“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
Findings Helpful for Counseling
Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”
There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.
A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.
To better understand how different clinical characteristics predict treatment needs, the researchers conducted a retrospective chart review of 234 patients who received a CNO diagnosis before age 18 and who established care in the Children’s Hospital Colorado’s CNO multidisciplinary clinic between January 2005 and July 2021. After excluding 70 patients, primarily due to inadequate follow-up for assessing treatment response, the researchers included 164 patients whose records they reviewed through January 2022.
The researchers assessed how multiple aspects of disease involvement, including unifocal or multifocal at diagnosis, ever having symmetric bone lesions, number of regions ever affected by CNO, complications, and disease activity at most recent follow-up, to determine their relationship to the total number of days on NSAID monotherapy and the odds of needing a second-line treatment.
Among the 164 patients in the study, 32 had a short course of NSAIDs (3-7 months), 62 had a long course of NSAIDs (7 or more months), and 70 received second-line treatment.
Findings From Largest Single-Center Cohort in North America
Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.
There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).
Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).
More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).
There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).
None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).
At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).
This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.
Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.
“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.
Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.
A version of this article appeared on Medscape.com .
CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.
Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.
CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.
“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
Findings Helpful for Counseling
Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”
There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.
A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.
To better understand how different clinical characteristics predict treatment needs, the researchers conducted a retrospective chart review of 234 patients who received a CNO diagnosis before age 18 and who established care in the Children’s Hospital Colorado’s CNO multidisciplinary clinic between January 2005 and July 2021. After excluding 70 patients, primarily due to inadequate follow-up for assessing treatment response, the researchers included 164 patients whose records they reviewed through January 2022.
The researchers assessed how multiple aspects of disease involvement, including unifocal or multifocal at diagnosis, ever having symmetric bone lesions, number of regions ever affected by CNO, complications, and disease activity at most recent follow-up, to determine their relationship to the total number of days on NSAID monotherapy and the odds of needing a second-line treatment.
Among the 164 patients in the study, 32 had a short course of NSAIDs (3-7 months), 62 had a long course of NSAIDs (7 or more months), and 70 received second-line treatment.
Findings From Largest Single-Center Cohort in North America
Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.
There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).
Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).
More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).
There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).
None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).
At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).
This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.
Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.
“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.
Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.
A version of this article appeared on Medscape.com .
FROM CARRA 2024
Tuberculosis Screening Gaps Persist in New DMARD Users
TOPLINE:
The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics.
METHODOLOGY:
- Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
- In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
- The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
- A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
- A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
- Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
- When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
- Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).
IN PRACTICE:
“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.
SOURCE:
The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research
LIMITATIONS:
The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.
DISCLOSURES:
This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics.
METHODOLOGY:
- Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
- In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
- The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
- A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
- A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
- Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
- When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
- Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).
IN PRACTICE:
“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.
SOURCE:
The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research
LIMITATIONS:
The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.
DISCLOSURES:
This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics.
METHODOLOGY:
- Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
- In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
- The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
- A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
- A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
- Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
- When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
- Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).
IN PRACTICE:
“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.
SOURCE:
The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research
LIMITATIONS:
The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.
DISCLOSURES:
This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
How Does Diet Affect Gastroesophageal Reflux Disease?
What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.
In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.
Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.
“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.
Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
Caloric Intake and Lipid Content
Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.
A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.
Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
The Role of Carbohydrates
While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.
Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.
A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.
A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.
Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
Questionable Studies
Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.
Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.
Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.
Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.
Dr. Zerbib reported no relevant financial conflicts related to his presentation.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.
In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.
Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.
“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.
Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
Caloric Intake and Lipid Content
Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.
A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.
Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
The Role of Carbohydrates
While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.
Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.
A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.
A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.
Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
Questionable Studies
Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.
Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.
Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.
Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.
Dr. Zerbib reported no relevant financial conflicts related to his presentation.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.
In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.
Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.
“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.
Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
Caloric Intake and Lipid Content
Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.
A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.
Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
The Role of Carbohydrates
While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.
Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.
A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.
A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.
Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
Questionable Studies
Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.
Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.
Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.
Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.
Dr. Zerbib reported no relevant financial conflicts related to his presentation.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.